Mechanotransduction by the Actin Cytoskeleton: Converting Mechanical Stimuli into Biochemical Signals
Abstract
Force transmission through the actin cytoskeleton plays a central role in cell movements, shape change, and internal organization. Dynamic reorganization of actin filaments by an array of specialized binding proteins creates biochemically and architecturally distinct structures, many of which are finely tuned to exert or resist mechanical loads. The molecular complexity of the actin cytoskeleton continues to be revealed by detailed biochemical assays, and the architectural diversity and dynamics of actin structures are being uncovered by advances in super-resolution fluorescence microscopy and electron microscopy. However, our understanding of how mechanical forces feed back on cytoskeletal architecture and actin-binding protein organization is comparatively limited. In this review, we discuss recent work investigating how mechanical forces applied to cytoskeletal proteins are transduced into biochemical signals. We explore multiple mechanisms for mechanical signal transduction, including the mechanosensitive behavior of actin-binding proteins, the effect of mechanical force on actin filament dynamics, and the influence of mechanical forces on the structure of single actin filaments. The emerging picture is one in which the actin cytoskeleton is defined not only by the set of proteins that constitute a network but also by the constant interplay of mechanical forces and biochemistry.
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Stress filaments consist of actin, myosin-II dimers, and associated crosslinkers.
“Stress filaments consist of actin, myosin-II dimers, and associated crosslinkers (Fig. 3c) [32–34].”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [34]
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BackgroundFeeling the force: formin’s role in mechanotransduction
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“After the activation and increase of integrin adhesions, their maturation into focal adhesions has been noted (Butcher et al. 2009; Harris et al. 2018).”
BackgroundElasticity of podosome actin networks produces nanonewton protrusive forces
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“Actin filaments are organized into diverse cytoskeletal structures by a wide range of actin-binding proteins (Michelot and Drubin, 2011; Harris et al., 2018).”
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“Since Actb is one of the major compo‐ nents of the cytoskeleton with a role in mechanotransduction [30], it is reasonable that it is particularly regulated in models with pronounced mechanical stress.”
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“Actin cytoskeleton rearrangement is necessary for the maintenance of force-induced cell shape [23, 24].”
BackgroundStructure, regulation, and mechanisms of nonmuscle myosin-2
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“Piconewton forces guide and direct the behavior of cells [184 ].”
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Cofilin-1 Is a Mechanosensitive Regulator of Transcription
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“In this process, actin, a prominent cyto-skeletal protein, operates as a mechanosensor, detecting and responding to external stimuli [102 – 104].”
BackgroundAnisotropic stretch biases the self-organization of actin fibers in multicellular Hydra aggregates
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“The cytoskeleton and associated proteins at focal adhesions are inherently mechanosensitive ( 45 – 48 ), and actin fibers formed, modified, or oriented by stress are present in other systems: ventral stress fibers in mammalian migrating cells ( 49 , 50 ), actin bundles in the development of…”
Spatial proximity of proteins surrounding zyxin under force-bearing conditions
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Strategies for advanced particulate bone substitutes regulating the osteo-immune microenvironment
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“The actin 424 cytoskeleton network is an interconnected and complex structure which is composed of a 425 dynamic interaction between different components, such as G-actin, F-actin, and actin-binding 426 mediators (121).”
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“44,45 In fact, the restricted growth of non-metastatic spheroids indicated by the decreased volume size observed in the experiments is consistent with our previous findings using a lower-resolution OCE system.”
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Unveiling the Intricate Connection: Cell Volume as a Key Regulator of Mechanotransduction
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“In general, the cytoskeltal network undergoes continuous growth and remodeling processes by means of filament polymerization and depolymerization in order to maintain homeostasis [22].”
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Modeling stem cell nucleus mechanics using confocal microscopy
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Registry Kinetics of Myosin Motor Stacks Driven by Mechanical Force-Induced Actin Turnover
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“Actin, like many other biological macromolecules, is mechanosensitive, in that its structural conformations are modulated by the mechanical forces acting on it (19).”
BackgroundElasticity of dense actin networks produces nanonewton protrusive forcesPreprint
Jasnin, M., Hervy, J., Balor, S., Bouissou, A., Proag, A., Voituriez, R., Maridonneau‐Parini, I., Baumeister, W. P., Dmitrieff, S., & Poincloux, R. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.13.439622 · Cited by 9 · see citing works
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The Shot CH1 domain recognises a distinct form of F-actin during Drosophila oocyte determination
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“Changes in the helical twist of F-actin filaments can be caused by mechanical tension, by interactions with actin-binding proteins (Harris et al., 2018; Jégou and Romet-Lemonne, 2020; Harris et al., 2020), or by the bending of F-actin filaments promoted by differences in the nucleotide states of actin monomers (Reynol…”
BackgroundThe Actomyosin Cortex of Cells: A Thin Film of Active Matter
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“The molecular field conjugate to (8) σ o = ν (”
BackgroundBiophysical cues involved in the stem cell niche for stemness maintenance
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An open-source combined atomic force microscope and optical microscope for mechanobiology studies
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Capturing ovarian dynamics through spatial profiling of the mechano-microenvironment
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Tissue-Informed Biomaterial Innovations Advance Pulmonary Regenerative Engineering
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Develop Tandem Tension Sensor to Gauge Integrin-Transmitted Molecular Forces
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“Mechano-transduction has a central role in cell migration, cell shape, and tissue morphogenesis by converting mechanical stimuli into biochemical responses acting through the actin cytoskeleton [33].”
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- Authors
- Harris, A. R., Jreij, P., & Fletcher, D. A.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Venue
- Annual Review of Biophysics
- Publisher
- Annual Reviews
- Published
- 2018-05-20
- Volume
- 47
- Issue
- 1
- Pages
- 617-631
- ISSN
- 1936-122X (ISSN-L)
- 1936-1238
- OpenAlex
- W2803134496
- Cited by
- 140
- References
- 101
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 19 · 2023: 14 · 2022: 14 · 2021: 24 · 2020: 25 · 2019: 15 · 2018: 3
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biophysics (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- mechanotransduction, actin cytoskeleton, mechanical forces, actin-binding proteins, actin filament dynamics, actin filament structure, force transmission, mechanical signal transduction, cytoskeletal structure, cell mechanics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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